We have previously shown that proliferating lymphoblastoid cells, as well as activated normal lymphocytes, contain an extractable protein (ADR) which is capable of inducing DNA synthesis in isolated quiescent nuceli. ADR is not secreted from the cell, and is not detectable in resting cells. The purpose of this research is to characterize and compare the molecular, physicochemical, and functional properties of this cytoplasmic factor extracted from a variety of neoplastic and normal cells. In addition, we are investigating the mechanism of action of ADR, as well as the control mechanisms which regulate its presence and/or activity. During the last fiscal year, we have made significant progress in a number of these areas. For example, we found that quiescent human lymphocytes contain a heat-stable protein which is capable of inhibiting the induction of DNA synthesis in resting nuclei by ADR derived from both normal and neoplastic sources. This inhibitor is also capable of suppressing ongoing synthetic activity in replicative nuclei from normal lymphocytes, but not from transformed lymphoblastoid cells. These results suggest that normal cells may maintain quiescence by cytoplasmic inhibitors, and that the loss of growth control in neoplastic cells may be due to a relative refractoriness of tumor cell nuclei to these factors. Progress in the last fiscal year also includes work on the locus of action of ADR (2D-PAGE analysis of iodinated nuclear membranes), as well as the development of specific T helper and suppressor cell clones to tetanus toxoid, to be used in studies on the generation and regulation of ADR in antigen-driven systems. (I)